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    Innate Killing of Leishmania donovani by Macrophages of the Splenic Marginal Zone Requires IRF-7

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    Author
    Phillips, R; Svensson, M; Aziz, N; Maroof, A; Brown, N; Beattie, L; Signoret, N; Kaye, PM
    Date
    2010-03-01
    Source Title
    PLoS Pathogens
    Publisher
    PUBLIC LIBRARY SCIENCE
    University of Melbourne Author/s
    Beattie, Lynette
    Affiliation
    Microbiology and Immunology
    Metadata
    Show full item record
    Document Type
    Journal Article
    Citations
    Phillips, R., Svensson, M., Aziz, N., Maroof, A., Brown, N., Beattie, L., Signoret, N. & Kaye, P. M. (2010). Innate Killing of Leishmania donovani by Macrophages of the Splenic Marginal Zone Requires IRF-7. PLOS PATHOGENS, 6 (3), https://doi.org/10.1371/journal.ppat.1000813.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/255854
    DOI
    10.1371/journal.ppat.1000813
    Abstract
    Highly phagocytic macrophages line the marginal zone (MZ) of the spleen and the lymph node subcapsular sinus. Although these macrophages have been attributed with a variety of functions, including the uptake and clearance of blood and lymph-borne pathogens, little is known about the effector mechanisms they employ after pathogen uptake. Here, we have combined gene expression profiling and RNAi using a stromal macrophage cell line with in situ analysis of the leishmanicidal activity of marginal zone macrophages (MZM) and marginal metallophilic macrophages (MMM) in wild type and gene targeted mice. Our data demonstrate a critical role for interferon regulatory factor-7 (IRF-7) in regulating the killing of intracellular Leishmania donovani by these specialised splenic macrophage sub-populations. This study, therefore, identifies a new role for IRF-7 as a regulator of innate microbicidal activity against this, and perhaps other, non-viral intracellular pathogens. This study also highlights the importance of selecting appropriate macrophage populations when studying pathogen interactions with this functionally diverse lineage of cells.

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